1*Medical Research Council International Nutrition Group, London School of Hygiene and Tropical Medicine, London, United Kingdom; Medical Research Council Unit, Banjul, The Gambia; Nutrition Research Institute, North Carolina Research Campus, Kannapolis, North Carolina, USA; Department of Nutrition, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA; University College London Genetics Institute, University College London, United Kingdom; Toxicology Services, Incorporated, Chapel Hill, North Carolina, USA; and Maternal and Child Nutrition Group, Medical Research Council Human Nutrition Research, Cambridge, United Kingdom.

2*Medical Research Council International Nutrition Group, London School of Hygiene and Tropical Medicine, London, United Kingdom; Medical Research Council Unit, Banjul, The Gambia; Nutrition Research Institute, North Carolina Research Campus, Kannapolis, North Carolina, USA; Department of Nutrition, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA; University College London Genetics Institute, University College London, United Kingdom; Toxicology Services, Incorporated, Chapel Hill, North Carolina, USA; and Maternal and Child Nutrition Group, Medical Research Council Human Nutrition Research, Cambridge, United Kingdom steven_zeisel@unc.edu.

Abstract

Choline is an essential nutrient, and the amount needed in the diet is modulated by several factors. Given geographical differences in dietarycholineintake and disparate frequencies of single-nucleotide polymorphisms (SNPs) in choline metabolism genes between ethnic groups, we tested the hypothesis that 3 SNPs that increasedependence on dietarycholine would be under negativeselection pressure in settings where choline intake is low: choline dehydrogenase (CHDH) rs12676, methylenetetrahydrofolate reductase 1 (MTHFD1) rs2236225, and phosphatidylethanolamine-N-methyltransferase (PEMT) rs12325817. Evidence of negativeselection was assessed in 2 populations: 1 in The Gambia, West Africa, where there is historic evidence of a choline-poor diet, and the other in the United States, with a comparatively choline-rich diet. We used 2 independent methods, and confirmation of our hypothesis was sought via a comparison with SNP data from the Maasai, an East African population with a genetic background similar to that of Gambians but with a traditional diet that is higher in choline. Our results show that frequencies of SNPs known toincreasedependence on dietarycholine are significantly reduced in the low-choline setting of The Gambia. Our findings suggest that adequate intake levels of choline may have to be reevaluated in different ethnic groups and highlight a possible approach for identifying novel functional SNPs under the influence of dietary selective pressure.-Silver, M. J., Corbin, K. D., Hellenthal, G., da Costa, K.-A., Dominguez-Salas, P., Moore, S. E., Owen, J., Prentice, A. M., Hennig, B. J., Zeisel, S. H. Evidence for negativeselection of genevariants that increasedependence on dietarycholine in aGambiancohort.